NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans

A M A  Murad; P  Leng; M  Straffon; J  Wishart; S  Macaskill; D  MacCallum; N  Schnell; D  Talibi; D  Marechal; F  Tekaia; C  d'Enfert; C  Gaillardin; F C  Odds; A J P  Brown

doi:10.1093/emboj/20.17.4742

NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans

A M A Murad, P Leng, M Straffon, J Wishart, S Macaskill, D MacCallum, N Schnell, D Talibi, D Marechal, F Tekaia, C d'Enfert, C Gaillardin, F C Odds, A J P Brown

Medical Sciences

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357 Citations (Scopus)

Abstract

We have characterized CaNrg1 from Candida albicans, the major fungal pathogen in humans. CaNrg1 contains a zinc finger domain that is conserved in transcriptional regulators from fungi to humans. It is most closely related to ScNrg1, which represses transcription in a Tup1-dependent fashion in Saccharomyces cerevisiae. Inactivation of CaNrg1 in C.albicans causes filamentous and invasive growth, derepresses hypha-specific genes, increases sensitivity to some stresses and attenuates virulence. A tup1 mutant displays similar phenotypes. However, unlike tup1 cells, nrg1 cells can form normal hyphae, generate chlamydospores at normal rates and grow at 42 degreesC. Transcript profiling of 2002 C.albicans genes reveals that CaNrg1 represses a subset of CaTup1-regulated genes, which includes known hypha-specific genes and other virulence factors. Most of these genes contain an Nrg1 response element (NRE) in their promoter. CaNrg1 interacts specifically with an NRE in vitro. Also, deletion of two NREs from the ALS8 promoter releases it from Nrg1-mediated repression. Hence, CaNrg1 is a transcriptional repressor that appears to target CaTup1 to a distinct set of virulence-related functions, including yeast-hypha morphogenesis.

Original language	English
Pages (from-to)	4742-4752
Number of pages	11
Journal	EMBO Journal
Volume	20
Issue number	17
DOIs	https://doi.org/10.1093/emboj/20.17.4742
Publication status	Published - 3 Sept 2001

Keywords

Candida albicans
NRG1 gene
transcript profiling
transcriptional repression
yeast-hypha morphogenesis
early growth-response
saccharomyces-cerevisiae
transcriptional repressor
catabolite repression
filamentous growth
escherichia-coli
finger-proteins
MIG1
SSN6-TUP1
promoter

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Murad, A. M. A., Leng, P., Straffon, M., Wishart, J., Macaskill, S., MacCallum, D., Schnell, N., Talibi, D., Marechal, D., Tekaia, F., d'Enfert, C., Gaillardin, C., Odds, F. C., & Brown, A. J. P. (2001). NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO Journal, 20(17), 4742-4752. https://doi.org/10.1093/emboj/20.17.4742

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title = "NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans",

abstract = "We have characterized CaNrg1 from Candida albicans, the major fungal pathogen in humans. CaNrg1 contains a zinc finger domain that is conserved in transcriptional regulators from fungi to humans. It is most closely related to ScNrg1, which represses transcription in a Tup1-dependent fashion in Saccharomyces cerevisiae. Inactivation of CaNrg1 in C.albicans causes filamentous and invasive growth, derepresses hypha-specific genes, increases sensitivity to some stresses and attenuates virulence. A tup1 mutant displays similar phenotypes. However, unlike tup1 cells, nrg1 cells can form normal hyphae, generate chlamydospores at normal rates and grow at 42 degreesC. Transcript profiling of 2002 C.albicans genes reveals that CaNrg1 represses a subset of CaTup1-regulated genes, which includes known hypha-specific genes and other virulence factors. Most of these genes contain an Nrg1 response element (NRE) in their promoter. CaNrg1 interacts specifically with an NRE in vitro. Also, deletion of two NREs from the ALS8 promoter releases it from Nrg1-mediated repression. Hence, CaNrg1 is a transcriptional repressor that appears to target CaTup1 to a distinct set of virulence-related functions, including yeast-hypha morphogenesis.",

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T1 - NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans

AU - Murad, A M A

AU - Leng, P

AU - Straffon, M

AU - Wishart, J

AU - Macaskill, S

AU - MacCallum, D

AU - Schnell, N

AU - Talibi, D

AU - Marechal, D

AU - Tekaia, F

AU - d'Enfert, C

AU - Gaillardin, C

AU - Odds, F C

AU - Brown, A J P

PY - 2001/9/3

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N2 - We have characterized CaNrg1 from Candida albicans, the major fungal pathogen in humans. CaNrg1 contains a zinc finger domain that is conserved in transcriptional regulators from fungi to humans. It is most closely related to ScNrg1, which represses transcription in a Tup1-dependent fashion in Saccharomyces cerevisiae. Inactivation of CaNrg1 in C.albicans causes filamentous and invasive growth, derepresses hypha-specific genes, increases sensitivity to some stresses and attenuates virulence. A tup1 mutant displays similar phenotypes. However, unlike tup1 cells, nrg1 cells can form normal hyphae, generate chlamydospores at normal rates and grow at 42 degreesC. Transcript profiling of 2002 C.albicans genes reveals that CaNrg1 represses a subset of CaTup1-regulated genes, which includes known hypha-specific genes and other virulence factors. Most of these genes contain an Nrg1 response element (NRE) in their promoter. CaNrg1 interacts specifically with an NRE in vitro. Also, deletion of two NREs from the ALS8 promoter releases it from Nrg1-mediated repression. Hence, CaNrg1 is a transcriptional repressor that appears to target CaTup1 to a distinct set of virulence-related functions, including yeast-hypha morphogenesis.

AB - We have characterized CaNrg1 from Candida albicans, the major fungal pathogen in humans. CaNrg1 contains a zinc finger domain that is conserved in transcriptional regulators from fungi to humans. It is most closely related to ScNrg1, which represses transcription in a Tup1-dependent fashion in Saccharomyces cerevisiae. Inactivation of CaNrg1 in C.albicans causes filamentous and invasive growth, derepresses hypha-specific genes, increases sensitivity to some stresses and attenuates virulence. A tup1 mutant displays similar phenotypes. However, unlike tup1 cells, nrg1 cells can form normal hyphae, generate chlamydospores at normal rates and grow at 42 degreesC. Transcript profiling of 2002 C.albicans genes reveals that CaNrg1 represses a subset of CaTup1-regulated genes, which includes known hypha-specific genes and other virulence factors. Most of these genes contain an Nrg1 response element (NRE) in their promoter. CaNrg1 interacts specifically with an NRE in vitro. Also, deletion of two NREs from the ALS8 promoter releases it from Nrg1-mediated repression. Hence, CaNrg1 is a transcriptional repressor that appears to target CaTup1 to a distinct set of virulence-related functions, including yeast-hypha morphogenesis.

KW - Candida albicans

KW - NRG1 gene

KW - transcript profiling

KW - transcriptional repression

KW - yeast-hypha morphogenesis

KW - early growth-response

KW - saccharomyces-cerevisiae

KW - transcriptional repressor

KW - catabolite repression

KW - filamentous growth

KW - escherichia-coli

KW - finger-proteins

KW - MIG1

KW - SSN6-TUP1

KW - promoter

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U2 - 10.1093/emboj/20.17.4742

DO - 10.1093/emboj/20.17.4742

M3 - Article

C2 - 11532938

SN - 0261-4189

VL - 20

SP - 4742

EP - 4752

JO - EMBO Journal

JF - EMBO Journal

IS - 17

ER -

NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans

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Keywords

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